title: Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver.
abstract: Leptin is one of the key molecules in maintaining energy homeostasis. Although genetically leptin-deficient Lep(ob)/Lep(ob) mice have greatly contributed to elucidating leptin physiology, the use of more than one species can improve the accuracy of analysis results. Using the N-ethyl-N-nitrosourea mutagenesis method, we generated a leptin-deficient Lep(mkyo)/Lep(mkyo) rat that had a nonsense mutation (Q92X) in leptin gene. Lep(mkyo)/Lep(mkyo) rats showed obese phenotypes including severe fatty liver, which were comparable to Lep(ob)/Lep(ob) mice. To identify genes that respond to leptin in the liver, we performed microarray analysis with Lep(mkyo)/Lep(mkyo) rats and Lep(ob)/Lep(ob) mice. We sorted out genes whose expression levels in the liver of Lep(mkyo)/Lep(mkyo) rats were changed from wild-type (WT) rats and were reversed toward WT rats by leptin administration. In this analysis, livers were sampled for 6 h, a relatively short time after leptin administration to avoid the secondary effect of metabolic changes such as improvement of fatty liver. We did the same procedure in Lep(ob)/Lep(ob) mice and selected genes whose expression patterns were common in rat and mouse. We verified their gene expressions by real-time quantitative PCR. Finally, we identified eight genes that primarily respond to leptin in the liver commonly in rat and mouse. These genes might be important for the effect of leptin in the liver.
authors.affiliation: Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Aizawa-Abe
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ebihara
authors.forename: Tomoji
authors.initials: T
authors.lastname: Mashimo
authors.forename: Akiko
authors.initials: A
authors.lastname: Takizawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tomita
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aotani
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamamoto-Kataoka
authors.forename: Takeru
authors.initials: T
authors.lastname: Sakai
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D018389:Codon, Nonsense; D004195:Disease Models, Animal; D005038:Ethylnitrosourea / Q000633:toxicity; D005234:Fatty Liver / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D020738:Leptin / Q000097:blood / Q000172:deficiency / Q000235:genetics* / Q000494:pharmacology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D009765:Obesity / Q000235:genetics*; D011922:Rats, Mutant Strains / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense; D020738:Leptin; D005038:Ethylnitrosourea
keywords: ENU mutagenesis; Lepmkyo/Lepmkyo rat; Lepob/Lepob mouse; leptin responsive gene; microarray analysis